CVS Corp. yesterday reached a milestone in its long trek toward becoming one of the nation’s largest companies, as shareholders of a Tennessee-based corporate giant agreed to sell to the Woonsocket-based drugstore chain.

Caremark Rx Inc., the nation’s second-largest pharmacy-benefits manager, approved a $27-billion takeover by CVS. The deal creates a behemoth with the heft to shape the country’s pharmacy marketplace at a time when Americans struggle with finding affordable health care.

With combined sales of more than $80 billion, the CVS/Caremark combination will rank among the top 20 companies in the current Fortune 500 — nearly dead-even with health-care organization supplier McKesson Corp. at number 16 and just ahead of Cardinal Health Inc., at number 19.

Winning a months-long fight for control of Caremark will help CVS cope with the effects of the new Medicare drug-benefit plan and fend off recent efforts by Wal-Mart to expand its pharmacy business, according to Wall Street analysts and industry consultants.

“The merger between CVS and Caremark is a revolutionary event within the health-care delivery network that should benefit payers, customers and shareholders alike,” said William Dreher, an analyst with Deutsche Bank in New York, in a note to clients.

Brishen Rogers, a lawyer with CtW Investment Group, which advises unions on investments, struggled to name another corporate battle that was as contentious as the fight between CVS and Express Scripts Inc., a rival pharmacy-benefits manager vying for control of Caremark.

“This was certainly one of the most hard-fought and difficult battles for control in recent years,” Rogers said. “At the end of the day, Caremark shareholders had a very tough choice here.”

The victory will have little immediate effect on the employment picture in Rhode Island, CVS executives have said. Jobs are expected to shift between Rhode Island and Tennessee, producing little change in the company’s work force in this state. CVS, the state’s biggest public company, currently employs 5,500 people in Rhode Island through its stores, corporate headquarters and distribution centers. It employs 176,000 nationwide.

CVS/Caremark Corp., as the company will be named, will be headquartered in Woonsocket. Tom Ryan, chairman, president and chief executive officer of CVS, will be the new company’s president and CEO. David Rickard, CVS’ chief financial officer, will take on the same role in the new company.

The pharmacy-benefit management portion of the company will be in Nashville, Tenn. — Caremark’s current home. Edwin “Mac” Crawford, Caremark’s chairman, will become chairman of CVS/Caremark.

Ryan, in a statement yesterday, said the company is ready to act on the promise executives made when they first proposed the merger in November.

“We have said from the beginning that this combination will transform the way pharmacy services are delivered, enabling consumers to benefit from enhanced health-care services and improved outcomes, and for payers to benefit from more effective cost-management tools,” Ryan said. “Now that we have obtained approval from both CVS and Caremark shareholders, we can begin delivering on this opportunity.”

Together, they will try to create a new entity in the health-care marketplace at a time when drugstores are fretting over the impact of mail-order prescription services and pharmacy-benefits managers worry about the pricing pressures squeezing them.

“The critical question is: ‘What does this transaction do for CVS strategically?’ ” Goldman Sachs analyst John Heinbockel said. “In short, becoming the largest [pharmacy-benefits manager] would greatly improve the company’s position to influence changes in the pharmacy marketplace.”

Pharmacy-benefits managers act as middlemen between drug makers and buyers such as health plans and drugstore chains, as well as administer much of the paperwork involved when people buy prescription drugs. By buying in bulk, pharmacy-benefits managers are supposed to help employers keep down health-care costs.

It’s a huge business: the managers handle 75 percent of the $235 billion Americans spend on prescriptions every year.

Caremark, PharmaCare (a CVS division), Medco Health Solutions Inc. — the nation’s largest pharmacy-benefits manager — and otherpharmacy-benefits managers counter rising costs by buying in bulk, often requiring patients to buy 90-day drug supplies. To boost profits, they’re also switching mail-order customers from higher-priced brand-name drugs to generics.

Much of the deal’s impact may be felt behind the scenes, as this new colossus muscles up against health insurers, drug makers, corporate clients and other retailers, industry consultants said.

Competitive pressures have gotten so intense, said Kim McDonough, president of Advanced Pharmacy Concepts in North Kingstown, that they’re pushing traditional rivals into each others’ arms. Wal-Mart’s move last fall to lower generic-drug prices is just the latest example.

“Historically, there’s not a real hunky-dory relationship between retail pharmacies and PBMs,” McDonough said.

Pharmacy-benefits managers have not been immune to pressure, particularly as the federal government gives itself a larger role in drug pricing, said Patrick Burns, of Taxpayers Against Fraud. The nonprofit advocacy group has been sharply critical of the effect these companies have had in the marketplace.

“PBMs have been a dinosaur waiting to go out of business,” said Burns, a spokesman for the consumer-advocacy group. “I believe that this CVS/Caremark merger is the process of this industry changing so completely that it will have a different definition.”

Founded in 1963, CVS has been moving to this point since at least 1996, the year it emerged from New York-based Melville Corp. as a standalone Rhode Island entity. The next year, the company bought the Revco drug chain in Ohio for $2.8 billion in a stock deal and began its drive to the top of the industry.

CVS had about $15 billion in sales and employed about 100,000 people by 1998.

In 2004, CVS took part in one of the largest deals in drugstore history — the purchase of J.C. Penney Co.’s Eckerd unit. CVS and Brooks Pharmacy (then headquartered in Warwick) paid a combined $4.6 billion for the chain. CVS took control of 1,260 Eckerd stores, 3 distribution centers and Eckerd’s pharmacy-benefit management business.

Last year, CVS bought 701 drugstores from Albertson’s Inc., in a multi-player transaction that made it the nation’s largest pharmacy chain in terms of stores — with about 6,100 outlets. CVS now has more stores than chief rival Walgreen’s.

As CVS grew, its headquarters and its control remained here — a rarity in Rhode Island companies. The last several years have seen control of one Rhode Island company after another move outside the state:

•In January, shareholders of American Power Conversion approved the company’s $6.1-billion sale to Schneider Electric SA, of France.

•That same month, RiteAid Corp. shareholders approved the Pennsylvania company’s purchase of the Warwick-based Brooks-Eckerd drugstore chain.

•Last August, lottery giant GTECH Holdings Corp. became a subsidiary of Rome-based Lottomatica SpA as part of a $4.8-billion deal.

• Rhode Island lost the headquarters of banking giant Fleet Financial Group shortly after the Providence company announced it was buying BankBoston Corp. in 1999. Even the name disappeared in 2004 when Bank of America Corp. bought FleetBoston Financial Corp.

•Citizens Financial Group Inc., based in Providence, has been an acquirer through the years, but even that company is owned by Royal Bank of Scotland.

CVS won its battle for control of Caremark after boosting its bid for a third time, offering to pay $54.74 a share, plus a one-time dividend of $7.50 a share, as it out-bid rival Express Scripts, of Maryland Height, Mo. CVS will also buy back 150 million of its own shares at $35 each.

Other parts of the original CVS/Caremark merger offer remain in place. Caremark shareholders will receive 1.67 shares of CVS/Caremark for each share of Caremark they own. CVS stockholders will own 54.5 percent of the new company and Caremark shareholders will own 45.5 percent.

The final bid came months after CVS announced plans to acquire Caremark for about $21.2 billion in stock. The drugstore chain had to boost its offer repeatedly since Express Scripts made an unsolicited $26-billion stock-and-cash bid. Caremark rejected that hostile bid.

Express Scripts eventually added about half a cent per share to its previous offer of $61.10 in cash and stock.

Caremark officials announced the results of the shareholders’ vote yesterday morning after concluding a 15-minute shareholder meeting in Nashville. The company didn’t immediately offer a detailed breakdown of the voting, pending certification by an inspector of elections.

The merger is expected to close next week, CVS and Caremark said.

pgrimald@projo.com